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Abstract The innate immune system is the first responder to infectious agents, cellular debris, and cancerous growths. This system plays critical roles in the antitumor immune responses by boosting and priming T cell-mediated cytotoxicity but is understudied due to the complexity and redundancy of its various downstream signaling cascades. We utilized a mathematical tool to holistically quantify innate immune signaling cascades and immunophenotype over 8,000 tumors from The Cancer Genome Atlas (TCGA). We found that innate immune activation was predictive of patient mortality in a subset of cancers. Further analysis identified PHF genes as transcripts that were associated with genomic stability and innate activation. Knockdown of PHF gene transcripts in vitro led to an increase in cell death and IFNB1 expression in a cGAS-dependent manner, validating PHF genes as potential anti-tumor targets. We also found an association between innate immune activation and both tumor immunogenicity and intratumor microbes, which highlights the versatility of this model. In conclusion, interrogating activation of innate immune signaling cascades demonstrated the importance of studying innate signaling in cancer and broadened the search for new therapeutic adjuvants.

Abstract Background Junior OB/GYN residents lack opportunities for fundamental surgical skills training of cesarean section, and most OB/GYN residents lack the experience of cervical laceration suturing due to its low incidence. Methods A porcine stomach simulation model was designed for obstetrics surgical training. The surface of the stomach simulated the uterus, and the pylorus and cardia simulated the cervical canal. Experience Materials are available from the nearby market. The total cost of the model is￥41. This model can be used in the training in uterus incision and repair of cesarean section and training in cervical laceration suturing. Conclusion The porcine stomach simulation model is pragmatic and realistic. They can be applied in the OB/GYN skill courses to introduce the fundamental obstetrics process to medical students and residents.

Abstract T cell senescence alters the homeostasis of distinct T cell populations and results in decayed adaptive immune protection in older individuals, but a link between aging and dynamic T cell clone changes has not been made. Here, using a newly developed computational framework, Repertoire Functional Units (RFU), we investigate over 6500 publicly available TCR repertoire sequencing samples from multiple human cohorts and identify age-associated RFUs consistently across different cohorts. Quantification of RFU reduction with aging reveals accelerated loss under immunosuppressive conditions. Systematic analysis of age-associated RFUs in clinical samples manifests a potential link between these RFUs and improved clinical outcomes, such as lower ICU admission and reduced risk of complications, during acute viral infections. Finally, patients receiving bone marrow transplantation show a secondary expansion of the age-associated clones upon stem cell transfer from younger donors. Together, our results suggest the existence of a ‘TCR clock’ that could reflect the immune functions in aging populations.

Abstract Background The persistent destructive power of cancer-related fatigue (CRF) has been regarded as the biggest influencing factor affecting the postoperative physical and mental health of patients with cervical cancer. During this process, patients might also experience different feelings of disease-related psychological. Therefore, this study aimed to adopt mindfulness-based stress reduction (MBSR) to intervene in patients with cervical cancer, and conducted follow-up for 3 and 6 months to observe the effects of changes in CRF, uncertainty in illness, coping styles, sense of coherence (SOC), and perceived social support (PSS). Methods A randomized controlled trial was conducted in ShengJing Hospital of China Medical University. A total of 102 patients were selected, and 78 patients completed the whole process, including 40 in the experimental group and 38 in the control group. Data were collected according to Cancer Fatigue Scale, Medical Coping Modes Questionnaire, Multidimensional Scale of Perceived Social Support, and Sense of Coherence-13. The change trend and difference of the two groups of research data were compared by repeated measurement analysis of variance. Bonferroni test was used for multiple tests between groups. Results The CRF, SOC, and coping styles of the MBSR group showed a decreasing trend (P

Abstract The activation of nuclear factor erythroid 2–related factor 2 (NRF2) has been observed in various cancers. Yet its exact contribution to the development of head and neck squamous cell carcinoma (HNSCC) remains undetermined. We previously found that NRF2 signaling is critical for the differentiation of squamous basal progenitor cells, while disruption of NRF2 causes basal cell hyperplasia. In this study, we revealed a correlation between elevated NRF2 activity and poor outcomes in HNSCC patients. We demonstrated that NRF2 facilitates tumor proliferation, migration, and invasion, as evidenced by both in vitro and in vivo studies. Significantly, NRF2 augments the expression of the antioxidant enzyme GPX2, thereby enhancing the proliferative, migratory, and invasive properties of HNSCC cells. Activation of GPX2 is critical for sustaining cancer stem cells (CSCs) by up-regulating NOTCH3, a key driver of cancer progression. These results elucidate that NRF2 regulates HNSCC progression through the NRF2-GPX2-NOTCH3 axis. Our findings proposed that pharmacological targeting of the NRF2-GPX2-NOTCH3 axis could be a potential therapeutic approach against HNSCC.

Lianhua Qingke tablets, a patented traditional Chinese medicine that has validated clinical efficacy for treating cough caused by severe acute respiratory syndrome coronavirus 2 infection, lack rigorous evidence-based research evaluating their effect on long coronavirus disease (COVID) cough. A randomized, double-blind, placebo-controlled, multicenter clinical study was conducted among patients with long COVID cough from 19 hospitals and 23 community health centers in China. Patients were randomized 1:1 to receive either Lianhua Qingke tablets or placebo orally for 14 days (four tablets, 1.84 g, three times a day). The primary endpoint indicator was the disappearance of cough, with the remission of cough also considered. Among 482 randomized patients, 480 (full analysis set 480; per-protocol set 470; safety set 480) were included in the primary analysis. According to the full analysis, the time until cough disappearance was significantly shorter in the trial group than in the control group, with a significant increase in the 14-day cough disappearance rate. Accordingly, the time to cough remission was significantly shorter in the trial group than in the control group. The change in the total symptom score was significantly greater in the trial group than in the control group on days 7 and 14, consistent with the results indicated by the visual analog scale (VAS) and cough evaluation test (CET) scores. No serious adverse events were recorded during the study. Lianhua Qingke tablets significantly improved the clinical symptoms of patients with long COVID cough.

Abstract Objective The aim of this study was to evaluate the effectiveness and safety of the nine most widely studied Vonoprazan (VPZ)-based treatment regimens along with traditional Proton pump inhibitor (PPI)-based treatment regimens in eradicating Helicobacter pylori (H. pylori) infection. Design Through searching PubMed, Embase, Cochrane Library, Web of Science, we exclusively included randomized controlled trials (RCTs) to investigate the efficacy of VPZ-based and PPI-based therapies for H. pylori infection. The included studies were evaluated for methodological quality using the Cochrane bias risk assessment tool, and the data analysis software was used to analyze the data accordingly. Results The RCTs were collected from the earliest available date up to August 2023. Twenty-one RCTs were included, with a total sample size of 5481. The results of the network meta-analysis showed that the eradication rate of the VPZ-based quadruple 14-day (VPZ-Q14) treatment regimen in Intention-to-treat (ITT) analysis was the highest (SUCRA: 0.874); The eradication rate of the VPZ-based quadruple 10-day (VPZ-Q10) treatment plan in Per-protocol (PP) analysis was the highest (SUCRA: 0.849). All regimens were well tolerated without significant differences. According to the probability ranking of safety, high-dose VPZ-based dual 14-day therapy (H-VPZ-D14) ranked first in SUCRA, reaching 0.952. This indicates that H-VPZ-D14 treatment is the safest with a relatively low incidence of adverse effect. Therefore, VPZ-based therapies not only have a higher eradication rate, but also possess satisfactory safety. Conclusion Compared with traditional PPI-based therapies, VPZ-based therapies have shown superior eradication effects. Based on the Ranking Plot of the Network, the VPZ-Q14 or VPZ-Q10 treatment regimen for H. pylori has a higher eradication rate and acceptable differences compared to other treatment regimens. In addition, for regions with high antibiotic resistance rates, we recommend a 14-day quadruple therapy with bismuth based on VPZ.

Abstract Multi-functional cysteine-targeting covalent warheads possess significant therapeutic potential in medicinal chemistry and chemical biology. Herein, we present novel unsaturated and asymmetric ketone (oxazolinosene) scaffolds that selectively conjugate cysteine residues of peptides and bovine serum albumin under normal physiological conditions. This unsaturated saccharide depletes GSH in NCI-H1299 cells, leading to anti-tumor effects in vitro. The acetyl group of the ketal moiety on the saccharide ring can be converted to other carboxylic acids in a one-pot synthesis. In this way, the loaded acid can be click-released during cysteine conjugation, making the oxazolinosene a potential multifunctional therapeutic agent. The reaction kinetic model for oxazolinosene conjugation to GSH is well established and was used to evaluate oxazolinosene reactivity. The aforementioned oxazolinosenes were stereoselectively synthesized via a one-step reaction of nitriles with saccharides and conveniently converted into a series of α, β-unsaturated ketone N-glycosides as prevalent synthetic building blocks. The reaction mechanisms of oxazolinosene synthesis were investigated through calculations and validated with control experiments. Overall, these oxazolinosenes can be easily synthesized and developed as cysteine-targeted covalent warheads carrying useful click-releasing groups.

Abstract Background The pretherapeutic differentiation of subtypes of primary intracranial germ cell tumours (iGCTs), including germinomas (GEs) and nongerminomatous germ cell tumours (NGGCTs), is essential for clinical practice because of distinct treatment strategies and prognostic profiles of these diseases. This study aimed to develop a deep learning model, iGNet, to assist in the differentiation and prognostication of iGCT subtypes by employing pretherapeutic MR T2-weighted imaging. Methods The iGNet model, which is based on the nnUNet architecture, was developed using a retrospective dataset of 280 pathologically confirmed iGCT patients. The training dataset included 83 GEs and 117 NGGCTs, while the retrospective internal test dataset included 31 GEs and 49 NGGCTs. The model’s diagnostic performance was then assessed with the area under the receiver operating characteristic curve (AUC) in a prospective internal dataset (n = 22) and two external datasets (n = 22 and 20). Next, we compared the diagnostic performance of six neuroradiologists with or without the assistance of iGNet. Finally, the predictive ability of the output of iGNet for progression-free and overall survival was assessed and compared to that of the pathological diagnosis. Results iGNet achieved high diagnostic performance, with AUCs between 0.869 and 0.950 across the four test datasets. With the assistance of iGNet, the six neuroradiologists’ diagnostic AUCs (averages of the four test datasets) increased by 9.22% to 17.90%. There was no significant difference between the output of iGNet and the results of pathological diagnosis in predicting progression-free and overall survival (P = .889). Conclusions By leveraging pretherapeutic MR imaging data, iGNet accurately differentiates iGCT subtypes, facilitating prognostic evaluation and increasing the potential for tailored treatment. Graphical Abstract

Abstract This article delves into Alzheimer’s disease (AD), a prevalent neurodegenerative condition primarily affecting the elderly. It is characterized by progressive memory and cognitive impairments, severely disrupting daily life. Recent research highlights the potential involvement of microRNAs in the pathogenesis of AD. MicroRNAs (MiRNAs), short non-coding RNAs comprising 20–24 nucleotides, significantly influence gene regulation by hindering translation or promoting degradation of target genes. This review explores the role of specific miRNAs in AD progression, focusing on their impact on β-amyloid (Aβ) peptide accumulation, intracellular aggregation of hyperphosphorylated tau proteins, mitochondrial dysfunction, neuroinflammation, oxidative stress, and the expression of the APOE4 gene. Our insights contribute to understanding AD’s pathology, offering new avenues for identifying diagnostic markers and developing novel therapeutic targets.

Abstract Underground cavities have complex spatial structures and geological settings, their arrangement is dense and crisscrossed. The construction system involves multiple work surfaces, levels, and processes. The close integration of construction simulation with actual production conditions is crucial for enhancing the guidance that simulation results provide for practical engineering. Therefore, from the perspective of optimizing construction organization and management, this article comprehensively considers various factors in the construction process, innovatively introduces the principle of production line balance and the concept of rule cycle, and combines technology and management, an underground cavities construction simulation system (UCCSS) is developed. In UCCSS, a hierarchical model is built and calculation are performed on models with different construction methods by modifying the parameters as per the actual engineering characteristics. The simulation results are comprehensively analysed to determine the optimal construction programme. An application case is proposed based on the construction organisation design of the long and parallel diversion tunnels at the CB Hydropower Station. The results show that the system has good practicality and credibility and can provide guidance for the construction organisation design of underground cavities with various features.

Abstract Background Numerous reports indicate that both obesity and type 2 diabetes mellitus (T2DM) are factors associated with cognitive impairment (CI). The objective was to assess the relationship between abdominal obesity as measured by waist-to-hip ratio adjusted for body mass index (WHRadjBMI) and CI in middle-aged and elderly patients with T2DM. Methods A cross-sectional study was conducted, in which a total of 1154 patients with T2DM aged ≥ 40 years were included. WHRadjBMI was calculated based on anthropometric measurements and CI was assessed utilizing the Montreal Cognitive Assessment (MoCA). Participants were divided into CI group (n = 509) and normal cognition group (n = 645). Correlation analysis and binary logistic regression were used to explore the relationship between obesity-related indicators including WHRadjBMI, BMI as well as waist circumference (WC) and CI. Meanwhile, the predictive power of these indicators for CI was estimated by receiver operating characteristic (ROC) curves. Results WHRadjBMI was positively correlated with MoCA scores, independent of sex. The Area Under the Curve (AUC) for WHRadjBMI, BMI and WC were 0.639, 0.521 and 0.533 respectively, and WHRadjBMI had the highest predictive power for CI. Whether or not covariates were adjusted, one-SD increase in WHRadjBMI was significantly related to an increased risk of CI with an adjusted OR of 1.451 (95% CI: 1.261–1.671). After multivariate adjustment, the risk of CI increased with rising WHRadjBMI quartiles (Q4 vs. Q1 OR: 2.980, 95%CI: 2.032–4.371, P for trend

Artificial intelligence generated content (AIGC) models have attracted widespread attention and application worldwide due to their excellent content generation capabilities. However, the rapid development of AIGC large models also brings a series of hidden dangers, such as concerns about interpretability, fairness, security, and privacy preservation of model-generated content. In order to reduce the unknowable risks and their harms, it becomes more and more important to carry out a comprehensive measurement and evaluation of AIGC large models. Academics have initiated AIGC large model evaluation studies aiming to effectively address the related challenges and avoid potential risks. This paper summarizes and analyzes the AIGC large model evaluation studies. Firstly, an overview of the model evaluation process is provided, covering model evaluation pre-preparation and corresponding measurement indicators, and existing measurement benchmarks are systematically organized. Secondly, the representative applications of the AIGC large model in finance, politics and healthcare and their problems are discussed. Then, the measurement methods are studied in depth through different perspectives, such as interpretability, fairness, robustness, security and privacy, and the new issues that need to be paid attention to AIGC large model evaluation are deconstructed, and the ways to cope with the new challenges of large model evaluation are proposed. Finally, the future challenges of AIGC large model evaluation are discussed, and its future development direction is envisioned.

Background As global population continues to age, disability has become one of the most prominent health problems in the aging population. Chinese older adults with chronic diseases often diagnosed with multi-morbidities resulting in increased risks for disability. However, previous evidence on disability rates in this population have been inconsistent. Objective To systematically evaluate the prevalence of disability in older adults with chronic diseases in China. Methods We searched databases including PubMed, Embase, Web of Science, Cochrane Library, Scopus, CNKI, Wanfang Data, VIP, CBM and China Medical Journal Full-text Database up until August 2023 for publications on disability prevalence in Chinese older adults with chronic diseases. Literature screening, quality appraisal and data extraction were performed independently by two researchers. Meta-analysis was conducted using Stata 16.0 software. Results A total of 32 publications (34 studies) were included. Sample sizes ranged from 221 to 16 566 cases with a disability rate of 6.9%-82.8%. Meta-analysis showed that the prevalence of disability in Chinese older adults with chronic diseases was 43.2% (95%CI=32.9%-53.5%). Subgroup analyses showed: disability rate was higher in female (36.6%, 95%CI=27.0%-46.2%) than in male (33.9%, 95%CI=23.9%-43.9%) ; disability prevalence increased with age (60-69 years old: 24.2%, 95%CI=14.3%-34.0%; 70-79 years old: 34.9%, 95%CI=24.1%-45.7%; ≥80 years old: 47.7%, 95%CI=36.3%-59.1%) ; compared to other chronic diseases, individuals with dementia/Parkinson's disease (56.3%, 95%CI=40.9%-71.7%), mental illness (53.9%, 95%CI=46.0%-61.7%), and cerebrovascular disease (49.2%, 95%CI=33.5%-64.8%) had the highest prevalence of disability; and the prevalence of disability increased with the number of comorbidities (1 disease: 33.1%, 95%CI=20.8%-45.3%; 2 diseases: 36.3%, 95%CI=22.6%-50.0%; ≥3 diseases: 49.7%, 95%CI=31.3%-68.0%) . Conclusion The prevalence of disability among Chinese older adults with chronic diseases is high and can be impacted by both the type of chronic disease and the number of comorbidities. It is recommended to strengthen chronic disease monitoring and management efforts to prevent and eliminate disability and promote healthy aging in this population.

Interactions between bone cells and neurocytes are crucial for endosseous nerve and ensuing bone regeneration. However, absence of neural stem cells in bone makes the innervation of implant osseointegration a major challenge. Herein, a nanorod-like array of sodium hydrogen titanate (ST) co-doped with Co2+ and Co3+, namely STCh that behaves as a reactive oxygen species (ROS)-scavenging enzyme, was hydrothermally formed on Ti substrate. We show that the doped Co2+ and Co3+ locate at TiO6 octahedral interlayers and within octahedra of STCh lattice, appearing releasable and un-releasable, respectively, leading to an increase in Co3+/Co2+ ratio and enzyme activity of the array with immersion. The nanoenzyme-released Co2+ triggers macrophages (MΦs) towards M1 phenotype, then the nanoenzyme scavenges extracellular ROS inducing M1-to-M2 transition. The neurogenic factors secreted by STCh-regulated MΦs, in combination with the released Co2+, promote mesenchymal stem cells to differentiate into neurons and Schwann cells compared to sole Co2+and ST. STCh array greatly enhances nerve reconstruction, type-H capillary formation and ensuing osseointegration in normal rat bone, and antibacteria via engulfing S. aureus by MΦs and osteogenesis in infective case. This nanoenzyme provides an alternative strategy to orchestrate endosseous nerve regeneration for osseointegration without loading exogenous neurotrophins in implants.

When tunnel boring machines (TBMs) excavate through jointed rock masses, the cutting efficiency is strongly affected by the shear strength of joints, the mechanism of which, however, remains poorly understood. In this study, a series of disc-cutter indentation tests were conducted on granite rock mass specimens with different joint shear strengths. During the indentation, the cracking process was recorded by a digital image correlation (DIC) system. The deformation and strength of specimens, cracking behavior, rock breakage mode and cutting efficiency were quantitatively investigated. In addition, to investigate the combined effects of joint shear strength, orientation and spacing on the rock breakage mechanism, numerical rock mass models were established based on a particle flow code PFC2D. Experimental results reveal that the cracking of primary and secondary cracks changes from the mixed shear-tensile to tensile mode in the initial stage, while the joint shear strength does not affect the cracking mode in the subsequent propagation process. The rock breakage mode is classified to an internal block breakage mode, a cross-joint breakage mode and a cutters-dependent breakage mode. The cross-joint breakage mode is optimal for improving the cutting efficiency. Numerical simulation results reveal that the increase in the joint shear strength changes the internal block breakage mode to cross-joint breakage mode for rock masses of particular ranges of joint orientation and spacing. These findings provide basis for improving the TBM cutting efficiency through jointed rock masses.

Extrachromosomal circular DNA (eccDNA) has recently gained increasing attention due to its significant role in cancer and other pathophysiologic states. The majority of circular DNAs detected by Circle-seq are small-size eccDNAs with enigmatic functions. One major technical hurdle is to synthesize eccDNA for functional identification. Here, we describe CAES (Circle-seq based Artificial EccDNA Synthesis), a promising and reliable method for artificial eccDNA synthesis. Eight eccDNAs carrying different microRNA genes (eccMIR) found in gastric cancer tissues, ranging from 329 bp to 2189 bp in size, were created utilizing the CAES method. Exonuclease V and single restriction-endonuclease digestion identified the circular structure of synthetic eccDNAs. The DNA circularization efficiency afforded by CAES ranged from 15.6% to 31.1%, which was negatively correlated with the eccDNA length. In addition, we demonstrated that CAES-synthesized eccMIRs can express both miRNA-3p and − 5p molecules efficiently independent of a canonical promoter in human cell lines. Further assays proved that these eccMIRs were functional as they were able to repress the luciferase gene containing a miRNA-target sequence in the 3′UTR as well as the endogenous mRNA targets. Finally, kinetics study revealed that eccDNA exhibited a decay rate similar to the standard plasmids and linear DNA in cultured cells. Together, this study offers a rapid and convenient method for Circle-seq users to synthesize artificial eccDNAs. It also demonstrates the promising potential of eccMIR as a bacterial DNA-free vector for safe and robust miRNA overexpression in both basic research and therapeutic applications.

Exogenous gibberellic acid was applied to regulate fruit growth of grapes to acquire high quality seedless berries. The vascular bundles provide the pathway of water and nutrient transport into the fruit and play an important role in berry growth and sugar accumulation. Therefore, changes in berry size and quality are closely related to the structure and function of the vascular tissue. In this study, 10-year-old “Shine Muscat” grape vines were treated with GA3 in grapevine production. Based on previous research and experimental environmental conditions, four treatments were applied: elongating cluster（5 mg L−1 GA3 on Apr. 28）+ seedless（25 mg L−1 GA3 on May. 24）+ expanding（50 mg L−1 GA3 on Jun. 7） (T1), seedless（25 mg L−1 GA3 on May. 24）+ expanding（50 mg L−1 GA3 on Jun. 7） (T2), expanding（50 mg L−1 GA3 on Jun. 7） (T3) and water (CK). Compared to CK, all fruits treated with GA3 had greater berry size. In addition, GA3 treated grapes had greater vascular bundle areas, including the areas of both phloem and xylem, as well as a greater number of vessels compared to control fruit. During the first rapid growth stage, water transport into the grape was rapid and did not differ among treatments. During veraison, the water transport rate among the four treatments differed, and the rank of speed was T2>T3>CK>T1. Therefore, we found that GA3 treatment can significantly promote the differentiation of vascular tissues and improve water transport capacity and phloem sugar unloading; T2 promoted the development of vascular bundles, enhanced water transport speed and phloem sugar unloading of fruit after veraison, and increased berry size.

Word of mouth (WOM) is crucial in customers’ purchasing decisions and affects companies’ long-term profits. This study examines the long-term trends in companies’ dynamic pricing and profits by using the Hamiltonian function method and dynamic simulation to construct a dynamic equation. It takes into account the intensity of word of mouth faced by companies and analyzes the level of publicity and consumers’ predictions of product quality. In this paper, we also discuss the interactive processes between WOM and advertising levels, the two most prominent market factors, and their ultimate impact on companies. The experimental results show that elevated levels of external advertising can potentially prompt companies to establish higher product pricing strategies, particularly in scenarios where the intensity of word of mouth is pronounced. In the initial phases of market development, the saturation level of consumers within the market exerts a negligible influence on companies’ long-term profit margins. Conversely, the rate of natural attrition from consumers’ upper threshold of product quality expectations distinctly impacts companies’ profitability.

Abstract Osteoarthritis (OA) is a chronic degenerative disease characterized by articular cartilage destruction and subchondral bone reconstruction in the early stages. Bergenin (Ber) is a cytoprotective polyphenol found in many medicinal plants. It has been proven to have anti-inflammatory, antioxidant, and other biological activities, which may reveal its potential role in the treatment of OA. This study aimed to determine the potential efficacy of Ber in treating OA and explore the possible underlying mechanism through network pharmacology and validation experiments. The potential co-targets and processes of Ber and OA were predicted by using network pharmacology, including a Venn diagram for intersection targets, a protein‒protein interaction (PPI) network to obtain key potential targets, and GO and KEGG pathway enrichment to reveal the probable mechanism of action of Ber on OA. Subsequently, validation experiments were carried out to investigate the effects and mechanisms of Ber in treating OA in vitro and vivo. Ber suppressed IL-1β-induced chondrocyte apoptosis and extracellular matrix catabolism by inhibiting the STAT3, NF-κB and Jun signalling pathway in vitro. Furthermore, Ber suppressed the expression of osteoclast marker genes and RANKL-induced osteoclastogenesis. Ber alleviated the progression of OA in DMM-induced OA mice model. These results demonstrated the protective efficacy and potential mechanisms of Ber against OA, which suggested that Ber could be adopted as a potential therapeutic agent for treating OA.

Abstract Sulfur deposition can result in an increase in the wall thickness of high-sulfur natural gas gathering pipelines, leading to issues like unstable pipeline flow. It is crucial to reveal the aggregation of sulfur particles at key locations of high-sulfur natural gas gathering pipelines to predict the location and amount of sulfur deposition in the pipelines. In this paper, the Euler–PBM (Population balance model) coupling is used to establish a numerical simulation model of gas–solid two-phase pipe flow accompanied by sulfur particle agglomeration in the pipe bends, focusing on the influence of sulfur particle volume fraction, pipe inclination angle and inlet flow velocity on sulfur particles agglomeration behavior. The results show that the sulfur particles have a significant agglomeration effect at the bend of the collecting pipeline, and the agglomeration growth occurs to different degrees throughout the bend, and the main area of sulfur particles agglomeration is near the top wall of the pipeline, followed by other areas near the wall of the pipeline. When the inlet volume fraction of sulfur particles was increased from 0.05 to 0.25%, and the inclination angle of the pipe was increased from 30° to 90°, the distribution range of sulfur particle size after agglomeration became wider, and the maximum size of sulfur particles was 187.56 μm, and the effect of sulfur particle agglomeration was enhanced; the inlet flow rate was increased from 3.0 to 9.0 m/s, and the reduction range of sulfur particle size after agglomeration was 5.68–9.87 μm. The maximum particle size of sulfur particles also decreased, and the effect of sulfur particle agglomeration was weakened.

Abstract The free-field switching of the perpendicular magnetization by the out-of-plane polarized spin current induced spin-orbit torque makes it a promising technology for developing high-density memory and logic devices. The materials intrinsically with low symmetry are generally utilized to generate the spin current with out-of-plane spin polarization. However, the generation of the out-of-plane polarized spin current by engineering the symmetry of materials has not yet been reported. Here, we demonstrate that paramagnetic CaRuO3 films are able to generate out-of-plane polarized spin current by engineering the crystal symmetry. The non-uniform oxygen octahedral tilt/rotation along film’s normal direction induced by oxygen octahedral coupling near interface breaks the screw-axis and glide-plane symmetries, which gives rise to a significant out-of-plane polarized spin current. This spin current can drive field-free spin-orbit torque switching of perpendicular magnetization with high efficiency. Our results offer a promising strategy based on crystal symmetry design to manipulate spin current and could have potential applications in advanced spintronic devices.

Abstract Background Clear cell odontogenic carcinoma (CCOC) is an odontogenic carcinoma characterized by sheets and islands of vacuolated and clear cells. The diagnosis of atypical CCOC can pose a challenge when tumor cells deviate from their characteristic clear morphology, even with the aid of genetic profiling for CCOC identification. Case presentation In this manuscript, we detailed the inaugural instance of a recurrently recurring clear cell odontogenic carcinoma (CCOC) with pronounced squamous differentiation in a 64-year-old male. The primary tumor in this individual initially displayed a biphasic clear cell phenotype. However, subsequent to the third recurrence, the clear tumor cells were entirely supplanted by epidermoid cells characterized by eosinophilic cytoplasm, vesicular chromatin, and prominent nucleoli. Notable aggressive attributes such as necrosis, conspicuous cytological malignancy, perineural dissemination, and vascular invasion were noted. Additionally, the tumor progressed to manifest lung metastases. The tumor cells exhibited positive immunoreactivity for AE1/AE3, KRT19, Pan-CK, EMA, P40, P63, CK34βE12, and P53, while they tested negative for CK35βH11, KRT7, S-100, and neuroendocrine markers. The Ki-67 proliferation index was calculated at an average of 15%. Furthermore, FISH analysis unveiled the presence of the EWSR1::ATF1 gene fusion. Conclusions This case illustrated a rare and aggressive case of CCOC characterized by significant squamous differentiation upon recurrence of the tumor.

Abstract The controversy surrounding whether serum total cholesterol is a risk factor for the graded progression of knee osteoarthritis (KOA) has prompted this study to develop an authentic prediction model using a machine learning (ML) algorithm. The objective was to investigate whether serum total cholesterol plays a significant role in the progression of KOA. This cross-sectional study utilized data from the public database DRYAD. LASSO regression was employed to identify risk factors associated with the graded progression of KOA. Additionally, six ML algorithms were utilized in conjunction with clinical features and relevant variables to construct a prediction model. The significance and ranking of variables were carefully analyzed. The variables incorporated in the model include JBS3, Diabetes, Hypertension, HDL, TC, BMI, SES, and AGE. Serum total cholesterol emerged as a significant risk factor for the graded progression of KOA in all six ML algorithms used for importance ranking. XGBoost algorithm was based on the combined best performance of the training and validation sets. The ML algorithm enables predictive modeling of risk factors for the progression of the KOA K–L classification and confirms that serum total cholesterol is an important risk factor for the progression of KOA.

Abstract Background Systemic conversion therapy provides patients with initially unresectable hepatocellular carcinoma (HCC) the chance to salvage radical liver resection and superior survival outcomes, but the optimal conversion strategy is unclear. Methods A systematic literature search was conducted on PubMed, EMBASE, Web of Science, Scopus, and the Cochrane Library between 2007 and 2024 focusing on studies reporting conversion therapy for HCC. The treatment groups were divided into Tyrosine kinase inhibitors (TKI), TKI plus loco-regional therapy (LRT), TKI plus anti-PD-1 therapy (TKI + PD-1), TKI + PD-1 + LRT, immune checkpoint inhibitors (ICI) plus LRT, and Atezolizumab plus bevacizumab (A + T) groups. The conversion to surgery rate (CSR), objective response rate (ORR), grade ≥ 3 treatment-related adverse events (AEs), overall survival (OS) and progression-free survival (PFS) were analyzed. Results 38 studies and 4,042 patients were included. The pooled CSR were 8% (95% CI, 5-12%) in TKI group, 13% (95% CI, 8-19%) in TKI + LRT group, 28% (95% CI, 19-37%) in TKI + PD-1 group, 33% (95% CI, 25-41%) in TKI + PD-1 + LRT group, 23% (95% CI, 1-46%) in ICI + LRT group, and 5% (95% CI, 3-8%) in A + T group, respectively. The pooled HR for OS (0.45, 95% CI, 0.35–0.60) and PFS (0.49, 95% CI, 0.35–0.70) favored survival benefit of conversion surgery. Subgroup analysis revealed that lenvatinib + PD-1 + LRT conferred higher CSR of 35% (95% CI, 26-44%) and increased ORR of 70% (95% CI, 56-83%). Conclusions The current study indicates that TKI + PD-1 + LRT, especially lenvatinib + PD-1 + LRT, may be the superior conversion therapy with a manageable safety profile for patients with initially unresectable HCC. The successful conversion therapy favors the superior OS and PFS compared with systemic treatment alone. Trial registration International prospective register of systematic reviews (PROSPERO) (registration code: CRD 42024495289).

Abstract Postpartum post-traumatic stress disorder (PP-PTSD) is a severe mental disorder worldwide. In recent years, some studies have reported that PP-PTSD stems from birth trauma. The present study was dedicated in finding ways to predict the occurrence of emergency caesarean section (ECS), trying to analyze the methods to reduce incidence of PP-PTSD on this basis, further exploring the neuroimaging changes in PP-PTSD. A total of 245 primiparas with intention of vaginal delivery were recruited. The internal tocodynamometry measurement was performed during labor for all mothers, and respectively taken at 3–5 cm, 5–8 cm, and 8–10 cm of cervical dilation. The receiver operating characteristic (ROC) curve and Binary logistic regression analyses were also performed to identify fetal head descending thrust that might help in the prediction of ECS. Resting-state magnetic resonance imaging (MRI) was performed on 26 patients diagnosed with PP-PTSD of 245 mothers, the amplitude of low-frequency fluctuations (ALFF) technology was used to observe the spontaneous neural activity of all PP-PTSD patients and correlation analyses were performed. We found that the natural delivery rate of mothers with fetal head descending thrust

Abstract Background Loneliness and social isolation have been found to be associated with various health-related outcomes. Our study aimed to evaluate the association of loneliness and social isolation with the risk of glaucoma. Methods A total of 373,330 participants from the UK Biobank without glaucoma at recruitment were included in this study. Self-reported questionnaires were used to define loneliness and social isolation. Incident glaucoma events were identified by hospital inpatient admissions and self-reported data. COX proportional hazards models adjusted for sociodemographic, lifestyle, and health-related factors were used to estimate hazard ratios (HRs) and 95% CIs. Results During a median follow-up of 13.1 (interquartile range: 12.3–13.9) years, 6,489 participants developed glaucoma. After adjusting for confounding factors, loneliness (yes vs. no: adjusted HR: 1.16; 95% CI: 1.04–1.30; P = 0.009) and social isolation (yes vs. no: adjusted HR: 1.08; 95% CI: 1.01–1.16; P = 0.033) were associated with an increased risk of glaucoma. Conclusions In this population-based prospective cohort study, loneliness and social isolation were associated with a higher risk of glaucoma.

To further develop a protein-polysaccharide composite fat replacer in low-fat meat products, this used pumpkin seed protein (PSP) and carrageenan to prepare a composite emulsion fat replacer, and added it to myofibrillar protein (MP) to form heat induced gel. The effects of the composite emulsion formed by PSP and carrageenan at various additive amounts on the properties of MP gels were investigated through the determination of gel moisture distribution, textural properties, microstructure, rheological properties, and other indexes. The results showed that when PSP and carrageenan composite emulsion was added at 50%, the water-holding properties and strength of the gel significantly improved (P

Abstract Mine water inflow is an important basis for the formulation of mining plans and the utilization of groundwater resources. The mine water inflow is the result of the combined influence of many factors. The weight value of the influencing factors is calculated by the entropy method, and the order of importance of the factors is: precipitation > mining depth > cumulative mined-out area > aquifer thickness > mining area > mining height. The optimal univariate nonlinear regression model of mine water inflow to each influencing factor is obtained by factor scatter analysis and Matlab function programming. On this basis, combined with the weight values of factors, a multivariate nonlinear regression prediction model of mine water inflow based on weighting is innovatively established, which overcomes the defect that the traditional water inflow prediction method that cannot reflect the relative importance differences of various influencing factors. The multivariate weighted nonlinear regression model is used to predict the mine water inflow of typical coal mines, and the prediction results are compared with the linear regression model and the measured value. The results show that the prediction model of mine water inflow based on weighted multivariate nonlinear regression is accurate higher, with higher practical application value.

Abstract It is of great significance to develop a novel approach to treat bacterial infections, as the frequent misuse of antibiotics leads to the serious problem of bacterial resistance. This study proposed antibiotic-free antibacterial nanoparticles for eliminating methicillin-resistant Staphylococcus aureus (MRSA) based on a multi-model synergistic antibacterial ability of chemodynamic therapy (CDT), photothermal effect, and innate immunomodulation. Specifically, a polydopamine (PDA) layer coated and Ag nanoparticles loaded core-shell structure Fe3O4 nanoparticles (Fe3O4@PDA-Ag) is prepared. The Fe3O4 catalyzes H2O2 present in acidic microenvironment of bacterial infection into more toxic reactive oxygen species (ROS) and synergizes with the released Ag ions to exert a stronger bactericidal capacity, which can be augmented by photothermal action of PDA triggered by near-infrared light and loosen the biofilm by photothermal action to promote the penetration of ROS and Ag ion into the biofilm, result in disrupting biofilm structure along with killing encapsulated bacteria. Furthermore, Fe3O4@PDA-Ag exerts indirect antibacterial effects by promoting M1 macrophage polarizing. Animal models demonstrated that Fe3O4@PDA-Ag effectively controlled MRSA-induced infections through photothermal enhanced CDT, Ag+ releasing, and macrophage-mediated bactericidal properties. The acid-triggered antibacterial nanoparticles are expected to combat drug-resistant bacteria infection. Graphical abstract

Abstract High-energy exciton emission could allow single-component multi-colour display or white light-emitting diodes. However, the thermal relaxation of high-energy excitons is much faster than the photon emission of them, making them non-emissive. Here, we report quantum dots with light hole-heavy hole splitting exhibiting strong high-energy exciton electroluminescence from high-lying light holes, opening a gate for high-performance multi-colour light sources. The high-energy electroluminescence can reach 44.5% of the band-edge heavy-hole exciton emission at an electron flux density Φ e of 0.71 × 1019 s−1 cm−2 − 600 times lower than the photon flux density Φ p (4.3 × 1021 s−1 cm−2) required for the similar ratio. Our simulation and experimental results suggest that the oscillator strength of heavy holes reduces more than that of light holes under electric fields. We attribute this as the main reason for strong light-hole electroluminescence. We observe this phenomenon in both CdxZn1-xSe-ZnS and CdSe-CdS core-shell quantum dots exhibiting large light hole-heavy hole splittings.

Abstract The continual large-scale urbanization and urban renewal in coastal cities of China have accumulated massive silty residue (SR) that may alter the coastal lines and always exerts high stresses to local environments. To meet China’s sustainable development policy, the need for green and high-efficient industrial treatments and reuse of SR is urgent. In this work, we may, for the first time, report a megaton-scale industrial project to upcycle low-quality SR and recycled aggregate (RA) to manufacture construction materials with hydrothermal mineralization (HM). In-situ pilot tests on five batches of SR-RA blocks were conducted. Results demonstrate that the produced blocks possess the compressive strengths of 11.4–15.8 MPa, densities of 1280–1430 kg/m3, porosities of 35–44%, CO2 emissions of 170.22–187.29 kg e-CO2/m3 and costs of 126.49–156.51 CNY/m3, comparable with or superior than the commercial blocks. The silica in SR could react with lime to produce tobermorite with stable pseudohexagonal plate under HM treatment, which improved the microstructure of the material. The findings validate the industrial practicability of upcycling low-quality SR and RA with HM for valuable construction block manufacture.

Abstract Background This dynamic nomogram model was developed to predict the probability of fetal loss in pregnant patients with systemic lupus erythematosus (SLE) with mild disease severity before conception. Methods An analysis was conducted on 314 pregnancy records of patients with SLE who were hospitalized between January 2015 and January 2022 at Shenzhen People's Hospital, and the Longhua Branch of Shenzhen People's Hospital. Data from the Longhua Branch of the Shenzhen People's Hospital were utilized as an independent external validation cohort. The nomogram, a widely used statistical visualization tool to predict disease onset, progression, prognosis, and survival, was created after feature selection using multivariate logistic regression analysis. To evaluate the model prediction performance, we employed the receiver operating characteristic curve, calibration curve, and decision curve analysis. Results Lupus nephritis, complement 3, immunoglobulin G, serum albumin, C-reactive protein, and hydroxychloroquine were all included in the nomogram model. The model demonstrated good calibration and discriminatory power, with an area under the curve of 0.867 (95% confidence interval: 0.787–0.947). According to decision curve analysis, the nomogram model exhibited clinical importance when the probability of fetal loss in patients with SLE ranged between 10 and 70%. The predictive ability of the model was demonstrated through external validation. Conclusion The predictive nomogram approach may facilitate precise management of pregnant patients with SLE with mild disease severity before conception.

Multi-principal component alloy has been proved to form disordered solid solution in most cases. However, multi-principal component alloy with single phase solid solution has a few disadvantages in mechanical properties, such as low strength or poor plasticity. Aiming at CoCrNi-based multi-principal component alloy with low strength, this paper proposed a method to enhance the multi-principal component alloy through composition design. CoCrNiVAlx multi-principal component alloy was melted by non-consumable vacuum arc melting, and the content of σ phase in the multi-principal component alloy was changed by adjusting the content of Al element. With the addition of Al element, the fcc disordered phase in the multi-principal component alloy gradually went to the ordered L12 phase with the same structure. When the amount of Al was 1.5 wt%, the compressive strength reached 2347 MPa and the hardness reached 760.8HV, which were 30% and 20% higher than the compressive strength (1828 MPa) and hardness (619.3HV) of CoCrNiV multi-principal component alloy, respectively. With the further increase of Al element to 2.0 wt%, the σ phase in the multi-principal component alloy increased further, resulting in the simultaneous decrease of strength and plasticity. The strengthening mechanism of multi-principal component alloy was analyzed, and the strengthening action of L12 phase was confirmed. The results showed that the strengthening of multi-principal component alloy was mainly provided by L12 phase strengthening (1229.55 MPa, 52.39%) and grain boundary strengthening (376 MPa, 16.02%). This paper provided a probable strategy to increase the strength of the multi-principal component alloy, which opened up a new idea for the composition design of multi-principal component alloy.

Abstract Magnons, bosonic quasiparticles carrying angular momentum, can flow through insulators for information transmission with minimal power dissipation. However, it remains challenging to develop a magnon-based logic due to the lack of efficient electrical manipulation of magnon transport. Here we show the electric excitation and control of multiferroic magnon modes in a spin-source/multiferroic/ferromagnet structure. We demonstrate that the ferroelectric polarization can electrically modulate the magnon-mediated spin-orbit torque by controlling the non-collinear antiferromagnetic structure in multiferroic bismuth ferrite thin films with coupled antiferromagnetic and ferroelectric orders. In this multiferroic magnon torque device, magnon information is encoded to ferromagnetic bits by the magnon-mediated spin torque. By manipulating the two coupled non-volatile state variables—ferroelectric polarization and magnetization—we further present reconfigurable logic operations in a single device. Our findings highlight the potential of multiferroics for controlling magnon information transport and offer a pathway towards room-temperature voltage-controlled, low-power, scalable magnonics for in-memory computing.

Abstract Purpose Good sleep is one of the necessary conditions to ensure the normal performance of the physiological and psychological functions of college students. This study aimed to explore the relationship between mobile phone addiction and bedtime procrastination among Chinese college students and the mediating mechanisms of physical exercise and anxiety between the two, with a view to seek ways to prevent and intervene in college students’ sleep procrastination and improve their sleep quality. Methods Using SPSS 29.0 analysis with Bootstrap’s method, 3,800 first-year students, sophomores, and juniors were given the Mobile Phone Addiction Tendency Scale, Bedtime Procrastination Scale, Physical Activity Scale, and Anxiety Scale. The results of the analyses included mediation tests and effect analyses of anxiety and physical activity. Results The correlation analysis revealed significant positive correlations between mobile phone addiction and bedtime procrastination (r = 0.149, p

Objective To explore the relationship between serum hypoxia inducible factor-1α (HIF-1α) and renal interstitial lesions in primary IgA nephropathy (IgAN). Methods From August 2017 to August 2021, retrospective analysis was performed for 142 IgAN patients. The relevant clinical data were collected and serum HIF-1αlevel was detected. They were divided into two groups according to the severity of renal interstitial lesions. Proportion of renal tubulointerstitial lesions ≤25% was mild group while >25% severe group. Inter-group differences in various parameters were examined by multiple factors. Correlations between serum HIF-1α and risk factors of kidney disease progression were analyzed. ResultsNo statistically significant inter-group differences existed in gender, 24 h urine protein quantification, body mass index (BMI), serum albumin, low-density lipoprotein cholesterol, triglycerides or hypertension (P>0.05). As compared with mild group, age [(44.45±9.65) year vs (38.36±11.09) year], blood creatinine [(116.28±44.75) μmol/L vs (84.82±42.06) μmol/L], blood uric acid [(389.03±104.57) μmol/L vs (353.39±90.01) μmol/L], serum HIF-1α[(213.53±68.86) pg/L vs (141.13±60.61) pg/L] were higher (P

Abstract Dental calculus severely affects the oral health of humans and animal pets. Calculus deposition affects the gingival appearance and causes inflammation. Failure to remove dental calculus from the dentition results in oral diseases such as periodontitis. Apart from adversely affecting oral health, some systemic diseases are closely related to dental calculus deposition. Hence, identifying the mechanisms of dental calculus formation helps protect oral and systemic health. A plethora of biological and physicochemical factors contribute to the physiological equilibrium in the oral cavity. Bacteria are an important part of the equation. Calculus formation commences when the bacterial equilibrium is broken. Bacteria accumulate locally and form biofilms on the tooth surface. The bacteria promote increases in local calcium and phosphorus concentrations, which triggers biomineralization and the development of dental calculus. Current treatments only help to relieve the symptoms caused by calculus deposition. These symptoms are prone to relapse if calculus removal is not under control. There is a need for a treatment regime that combines short-term and long-term goals in addressing calculus formation. The present review introduces the mechanisms of dental calculus formation, influencing factors, and the relationship between dental calculus and several systemic diseases. This is followed by the presentation of a conceptual solution for improving existing treatment strategies and minimizing recurrence.

Abstract Water ice and other volatiles that accumulated in the Moon’s polar regions are among the top priority targets for lunar exploration, due to their significances in both lunar geology and extraterrestrial resource utilization. Locating suitable landing sites and determining the provenance of sampled/measured surface materials are critical for future landed missions. Here, we map over 800 sites of plains terrains in the Moon’s south polar region, with a total surface area of ~46,000 km2. Orbital measurements and analog studies show that most of these plains have apparently higher albedo and lower iron content than volcanic mare plains, suggesting an origin of ejecta-induced debris flows from distant impact craters, especially from the Schrödinger basin. Our findings suggest that the entire lunar south polar region probably have experienced contributions from distant basin materials. We recommend these plains as priority landing sites for future exploration of lunar polar volatiles and early bombardment history.

Abstract Background Limited studies have investigated the correlation between fat distribution and the risk of diabetic retinopathy (DR) in the general population with diabetes. The relationship between obesity and DR remains inconclusive, possibly due to using simple anthropometric measures to define obesity. This study investigates the relationships between the android-to-gynoid fat ratio (A/G ratio, measured using dual-energy X-ray absorptiometry) and DR within the US population with diabetes. Methods The study used a population-based, cross-sectional approach based on the 2003–2006 and 2011–2018 data of the National Health and Nutrition Examination Survey (NHANES). Multivariable logistic regression analyses were performed on participants with diabetes to evaluate the contribution of body mass index (BMI), waist-to-height ratio (WHtR), and A/G ratio to the prevalence of DR. Results The prevalence of DR was 22.2, 21.2, and 17.6% among participants with A/G ratios

Abstract Currently, deep learning methods for low‐light image enhancement tasks mainly focus on the illumination of images, while neglecting the problems of image noise and feature loss. To address this issue, this paper proposes a novel low‐light image enhancement network called DAF‐Retinex, based on the Retinex‐Net. To address the issue of image noise, different from traditional image denoise methods, this paper utilizes a fully convolutional neural network to denoise the reflection component, additionally, a denoising loss function is introduced to suppress noise. For preserving image details and extracting features, this paper creatively introduces self‐calibrated convolutions into low‐light image enhancement tasks, furthermore, a feature augmented attention block consisting of feature‐guided attention (FGA) is designed for feature learning to effectively enhance image illumination and extract image detail features. Experimental results demonstrate that the proposed algorithm in this paper effectively removes image noise and extracts detailed features, resulting in visually improved outcomes. On public datasets, the average improvement in objective evaluation metrics of image quality such as PSNR, SSIM, and NIQE are 1.13%, 4.12%, and 1.28%, respectively.

Objective In orthopedic trauma, identification of extremity trauma combined with vascular injury is challenging. Missed diagnosis may result in amputation or even death. The purpose of this study was to investigate whether physical examination combined with handheld vascular ultrasound Doppler examination could be an effective method of screening for peripheral vascular injury and to explore the characteristics of vascular injuries in orthopedic trauma patients. Methods Retrospective analysis of patients in the emergency department of orthopedic trauma in our hospital from January 2022 to October 2023. Physical examination combined with handheld vascular ultrasound Doppler examination was used as a screening method for suspected vascular injuries. Patients with suspected vascular injury would undergo further angiography and receive multidisciplinary treatment. Angiography was used as the gold standard for diagnosing vascular injuries. Patient demographics, mechanism of injury, location and type of injury, angiographic results, surgical notes, and early treatment outcome data were recorded. Results A total of 55 cases (58 limb injuries) with suspected vascular injury were ultimately included. Angiography revealed that 53 cases (55 limbs, positive rate 94.8%) were considered to have confirmed vascular injuries. Forty‐three were male (81.1%) and 10 were female (18.9%), with mean age 44.1 ± 16.6 years. The main mechanism of injury was traffic accident (30, 56.7%). Most common site of vascular injuries was knee joint (30/55, 54.5%), and popliteal artery (23, 47.9%) was the most commonly injured blood vessel. After multidisciplinary collaborative treatment, overall patient mortality was 3.8% (2/53), and limb survival rate among surviving patients was 81.1% (43/53) in our study. Conclusion In orthopedic trauma, “Hard signs” and “soft signs” combined with handheld vascular ultrasound Doppler examination were effective ways to screen for suspected vascular injuries. Most limbs had associated fractures or dislocations at the site of vascular injury. Collaboration of vascular surgery, microsurgery and orthopedic trauma may help improve patients' prognosis.